From Molecules to Systems: Towards an Integrated Heuristic for Understanding the Physics of Life

在过去的50年里，我们在最基本的分子水平上对生物学的理解取得了巨大的进步。例如，DNA的结构已经被发现，其结构中编码的遗传信息已经开始被计算出来。我们知道，许多生物分子与较大生物体中的特定类型的行为有关：例如，一些人对特定疾病具有遗传易感性。然而，理解细胞内单个分子与人的行为之间的链中的复杂联系是一个非常困难的挑战。我们可以专注于单个分子并非常详细地了解它们的结构和行为，但每个人体包含大量不同类型的分子，挑战是试图将每个细胞内发生的分子之间相互作用的复杂系统组合在一起；导致组织功能的细胞之间的关系；以及组织和器官整合为一个完整的人的方式。例如，当一个人发现自己患有癌症时，疾病很有可能是从单个分子的变化开始的；但这将启动一系列令人震惊的复杂的因果链条，从而导致疾病的形成，现代表观遗传学也表明，复杂的因果链很可能在最初的变化之前就已经开始了。解开这种相互作用的网络是一个巨大的挑战，但这无疑是目前生物学面临的最重要的问题。显然，生物系统在不同的长度尺度上发挥作用(分子/细胞/组织/人)，挑战是整合跨长度尺度的理解。例如，生物学家思考分子的方式与他们思考生态系统的方式非常不同，尽管一个分子事件可能会引发生态系统的变化。多年来，物理学一直在解决跨长度尺度积分的问题。在最极端的情况下，量子引力试图将量子力学(处理物质的最小组成部分)和广义相对论(描述行星、恒星和星系的行为)的定律结合起来。重要的是，物理学家们一直在考虑细节，以及如何跨长度尺度进行整合，以绘制出一幅非常大的系统的图景。我们相信，这给了物理学家独特的洞察力，可能也会帮助生物学家整合他们在长度尺度上的思维。这个网络计划的目标是促进物理学家和生物学家之间的接触，共同应对这一重要挑战。网络将提供一系列活动，旨在帮助物理学家和生物学家建立新的合作伙伴关系，致力于寻找一个框架来理解整个长度尺度的生物学。最初的三个活动将聚焦于关键挑战(许多分子如何聚集在一起形成一个活细胞？我们能否建立复制细胞行为的合成系统，并让我们了解从分子到细胞的整合是如何运作的？许多细胞如何在组织、生物膜或其他形式中协同工作？)在这些初始事件之后，将开展一系列活动，以提供将领先的物理学家和生物学家聚集在一起应对已确定的重要挑战的手段。我们的目标将是提供一个框架，在此框架内，物理学家和生物学家可以在整个长度范围内合作理解生物学。这一努力的回报很多，包括更好地了解疾病(例如癌症)、生态系统和环境、光合作用和生物能量收集、生物技术和生物膜。这将不可避免地为英国许多与生物科学相关的行业以及公民的健康和生活质量做出重大贡献。

The last fifty years have seen enormous strides in our understanding of biology at the most basic level, the molecular scale. For example, the structure of DNA has been discovered, and the genetic information encoded in its structure has begun to be worked out. We know that many biological molecules are associated with particular types of behaviour in larger organisms: for example some people have a genetic predisposition to particular diseases. However, understanding the complex links in the chain between a single molecule inside a cell and the behaviour of a person is a very difficult challenge. We can focus in on individual molecules and understand their structures and behaviour in great detail, but every human body contains vast numbers of molecules of many different types, and the challenge is to try to put together the complex systems of interactions between molecules that go on inside each cell; the relationships between cells that lead to the function of tissue; and the way that tissues and organs are integrated into a whole person. When a person discovers they have cancer, for example, there is a strong chance that the disease began with a change in a single molecule; but this will have initiated a staggeringly complex cascade of knock-on chains of cause-and-effect that led to the formation of the disease, and modern epigenetics is also suggesting that a complex chain of cause-and-effect may very well have preceded that initial change. Untangling this web of interactions is an enormous challenge but it is undoubtedly the most important problem facing biology at present.It is clear that biological systems function on different length scales (molecules/cells/tissues/people) and the challenge is to integrate understanding across the length scales. The ways that biologists think about molecules are very different from the ways that they think about ecosystems, for example, even though a molecular event can trigger a change in an ecosystem. Physics has been addressing the problem of integrating across length scales for many years. At the most extreme, quantum gravity tries to integrate the laws of quantum mechanics (which deals with the smallest building blocks of matter) and general relativity (which describes the behaviour of planets, stars and galaxies). Importantly, physicists have been thinking about detail and also how to integrate across length scales to develop a picture of very large systems. We believe that this gives physicists unique insights that may potentially help biologists to integrate their thinking across the length scales too. The goal of this Network proposal is to stimulate engagement between physicists and biologists to tackle this important challenge together.The Network will provide a range of activities designed to help physicists and biologists build new partnerships devoted to finding a framework to understand biology across the length scales. Three initial events will focus on key challenges (How do many molecules come together to form a living cell? Can we build synthetic systems that replicate cell behaviour and allow us to understand how the integration from molecules to cells functions? How do many cells work together in tissue, biofilm or other forms?) Following these initial events a series of activities will be developed to provide the means of bringing leading physicists and biologists together to address the important challenges identified.Our goal will be to provide a framework from within which physicists and biologists can work together to understand biology across the length scales. The rewards for this effort are many, including the development of a better understanding of disease (for example, cancer), ecosystems and the environment, photosynthesis and biological energy harvesting, biotechnology and biofilms. Inevitably this will contribute substantially to the many bioscience-related industries in the UK and to the health and quality of life of its citizens.